ArticleAmerican journal of respiratory cell and molecular biology2019
Glutaminolysis Epigenetically Regulates Antiapoptotic Gene Expression in Idiopathic Pulmonary Fibrosis Fibroblasts.
Article in American journal of respiratory cell and molecular biology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 62 papers, 1 of them a synthesis that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
62 citing papers in PubMed, 1 synthesis or guideline pooled it, 80 citations in OpenAlex.
- Genetic liability of gut microbiota for idiopathic pulmonary fibrosis and lung function: a two-sample Mendelian randomization study.Frontiers in cellular and infection microbiology · 2024Pooled it
- Bacillus-based probiotics ameliorate bleomycin-induced pulmonary fibrosis in rats: coupling intestinal barrier reinforcement to the modulation of M2 macrophage polarization/TGF-β/p38MAPK and inflammasome-driven pyroptosis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Mechanosignaling promotes macrophage apoptosis resistance in pulmonary fibrosisbioRxiv : the preprint server for biology · 2026Article
- Advances in metabolic reprogramming of pulmonary fibrosis.Chinese medical journal pulmonary and critical care medicine · 2026Review
- The Gut-Lung Microbiome Axis in Alveolar Stem Cell Regeneration and Lung Repair.Microorganisms · 2026Review
- Fibroblasts as regulators of lung immunity, repair and fibrosis.Nature reviews. Immunology · 2026Review
- Intestinal dysbiosis associates with silica-induced pulmonary fibrosis in mice via arginine and tryptophan pathways.BMC microbiology · 2026Article
- The role of glutamine metabolism in the pathogenesis of idiopathic pulmonary fibrosis and its therapeutic potential.Frontiers in oncology · 2026Review
- Reprogrammed Fibrotic Niche Fuels Lung Cancer Initiation and Reciprocal Remodeling.International journal of biological sciences · 2026Review
- Metabolic dysregulation in pulmonary fibrosis: insights into amino acid contributions and therapeutic potential.Cell death discovery · 2025Review
- Review
- The Sound of Silence: Suppressing CBX5 Decreases Fibrosis by Inhibiting Fibroblasts.American journal of respiratory cell and molecular biology · 2025Article
- Succinate aggravates pulmonary fibrosis through the succinate/SUCNR1 axis.American journal of physiology. Lung cellular and molecular physiology · 2025Article
- Tanshinone IIA alleviates pulmonary fibrosis by modulating glutamine metabolic reprogramming based on [U-Journal of advanced research · 2025Article
- Association between genetic prediction of 486 blood metabolites and the risk of idiopathic pulmonary fibrosis: A mendelian randomization study.Biomedical reports · 2025Article
- Triangle correlations of lung microbiome, host physiology and gut microbiome in a rat model of idiopathic pulmonary fibrosis.Scientific reports · 2024Article
- Micro-RNAs in breast cancer progression and metastasis: A chromatin and metabolic perspective.Heliyon · 2024Review
- Anti-Heat Shock Protein 70 Autoantibodies from Patients with Idiopathic Pulmonary Fibrosis Epigenetically Enhance Lung Fibroblast Apoptosis Resistance and Bcl-2 Expression.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Causal relationship between circulating glutamine levels and idiopathic pulmonary fibrosis: a two-sample mendelian randomization study.BMC pulmonary medicine · 2024Article
- Review
2 more citing papers are in PubMed but not listed here.
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Authors and funding
7 authors at 3 institutions in 2 countries.
Funding
Abstract
Fibrotic responses involve multiple cellular processes, including epigenetic changes. Epigenetic changes are sensitive to alterations in the tissue microenvironment such as the flux of tricarboxylic acid (TCA) cycle metabolites. TCA metabolites directly regulate epigenetic states, in part by regulating histone modification-related enzymes. Glutaminolysis is a critical metabolic process by which glutamine is converted to glutamate by glutaminase and then to α-ketoglutarate (α-KG), a TCA cycle metabolite. Idiopathic pulmonary fibrosis (IPF) is a disease characterized by aberrant metabolism, including enhanced glutaminolysis. IPF fibroblasts are apoptosis resistant. In this study, we explored the relationship between glutaminolysis and the resistance to apoptosis of IPF fibroblasts. Inhibition of glutaminolysis decreased expression of XIAP and survivin, members of the inhibitor of apoptosis protein (IAP) family. α-KG is a cofactor for JMJD3 histone demethylase, which targets H3K27me3. In the absence of glutamine, JMJD3 activity in fibroblasts is significantly decreased, whereas H3K27me3 levels are increased. Chromatin immunoprecipitation assays confirmed that JMJD3 directly interacts with XIAP and survivin promoter regions in a glutamine-dependent manner. Exogenous α-KG partially restores JMJD3 function and its interaction with the XIAP and survivin promoter regions under glutamine-deficient conditions. Interestingly, α-KG upregulates XIAP, but not survivin, suggesting differential α-KG-dependent and -independent mechanisms by which glutamine regulates these IAPs. Our data demonstrate a novel mechanism of metabolic regulation in which glutaminolysis promotes apoptosis resistance of IPF fibroblasts through epigenetic regulation of XIAP and survivin.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.